Phthalonitrile

Endpoint summary

Description of key information

O-phthalonitrile is toxic after acute oral application. Since ortho-phthalonitril is supposed to be  toxic via all routes of exposure, classification for acute inhalation and dermal toxicity was adopted for precautionary reasons.  

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is comparable to OECD 401 with acceptable restrictions mostly due to reduced reporting in times before GLP.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: US

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeder
- Mean weight at study initiation: 200 +- 23 g (male), 156 +- 8 (female)

ENVIRONMENTAL CONDITIONS
not reported

Route of administration:

oral: gavage

Vehicle:

other: aqueous emulsion with traganth

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.5% - 2%

MAXIMUM DOSE VOLUME APPLIED: 16 mL/kg = maximum 3.7 mL per male and 2.6 mL per female animal, respectively

Doses:

50, 100, 125, 160 and 200 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 7/14 days
- Frequency of observations and weighing: Weighing was performed only at the beginning of the study. Observation of clinical signs was several times on the day of administration and once daily afterwards except on weekends and on holidays.
- Necropsy of survivors performed: yes

Statistics:

Not performed.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 125 mg/kg bw

Mortality:

200 mg/kg: 10/10 animals died within 24 hrs after application
160 mg/kg: 8/10 animals died within 24 hrs after application
125 mg/kg: 4/10 animals died within 24 hrs after application
100 mg/kg: 1/10 animals died within 24 hrs after application
50 mg/kg: no mortality

Clinical signs:

other: 100 - 200 mg/kg: directly after application: agitation, accelerated and partly intermittent respiration, clonic convulsions, cry of pain, Straub tail phenomenon ("Morphinschwanz"), oral secretion, ruffled, fluffed fur. Symptoms started to decrease slowly

Gross pathology:

Animals that died
Strong dilatation of the gastrointestinal tract, clear test substance odor, kidney congestion, 1x bloody congested lung, serous or bloody serous smeared snouts in all animals, 1x thorax tissue layers filled with liquid , 4x terminal blood congestion of the lung and the liver, 1x lung edema

Sacrificed animals
Nothing abnormal found

LC0 = 50 mg/kg

Executive summary:

The study was comparably performed according to OECD 401 with acceptable restrictions mostly due to reduced reporting in times before GLP. Groups of 5 rats per sex and dose were administered 50, 100, 125, 160 and 200 mg/kg of the test substance. The acute LD50 for male and female rats is ca. 125 mg/kg. Clonic convulsions, Straub tail phenomenon, oral secretion, waddling gait and lung edema in one animal that died were observed.

Conclusion

O-phthalonitrile is toxic after acute oral application (R25 following EU classification requirements and Cat. 3 following GHS criteria).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

125 mg/kg bw

Additional information

An acute oral toxicity study comparably to OECD 401 with acceptable restrictions mostly due to reduced reporting in times before GLP was preformed. Groups of 5 rats per sex and dose were administered 50, 100, 125, 160 and 200 mg/kg of the test substance. The acute LD50 for male and female rats is ca. 125 mg/kg. Clonic convulsions, Straub tail phenomenon, oral secretion, waddling gait and lung edema in one animal that died were observed (BASF, 1969).

Justification for classification or non-classification

O-phthalonitrile is toxic after acute oral administration (acute oral cat. 3 ). Since ortho-phthalonitril is supposed to be toxic via all routes of exposure, classification for acute inhalation and dermal toxicity was adopted for precautionary reasons. (acute inhal cat 3, acute dermal cat 3).